Investigation of four (99m)Tc-labeled bacteriophages for infection-specific imaging.

Abstract

INTRODUCTION:

This study investigated radiolabeled bacteriophages for specific detection of infection through gamma imaging. Previously, a (99m)Tc-labeled M13 phage demonstrated specific binding for its host Escherichia coli in vitro and in mice through imaging.

METHODS:

This study was extended to phages P22, E79, VD-13 and phage 60. Each was radiolabeled with (99m)Tc using the chelator MAG(3), and were evaluated for binding to host and non-host bacteria in vitro and in a mouse infection model.

RESULTS:

In vitro, each (99m)Tc-phage bound to its host at least 4-fold higher than to non-host bacteria. For example, (99m)Tc-E79 showed 10- to 20-fold greater binding to host Pseudomonas aeruginosa compared to non-host Escherichia coli and Salmonella enterica, and (99m)Tc-phage 60 showed 20-fold greater binding to host Klebsiella pneumoniae over non-hosts. Mice received host or non-host bacteria in one thigh, and 3 h later, the (99m)Tc-phages were administered intravenously. After a further 3 h, the tissues were counted. Liver accumulation was highest for (99m)Tc-E79, averaging 39% compared to an average of 13% for the other (99m)Tc-phages. Animals infected with host bacteria showed infected thigh/normal thigh ratios of 14.2 for (99m)Tc-E79, 2.9 for (99m)Tc-P22, 3.5 for (99m)Tc-VD-13 and 2.1 for (99m)Tc-phage 60.

CONCLUSIONS:

Although specific host binding was observed in vitro for each of these four (99m)Tc-phages, only (99m)Tc-E79 showed specificity for its host in an in vivo model.

• Authors: Mary Rusckowski, Suresh Gupta, Guozheng Liu, Shuping Dou, Donald J Hnatowich
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 35 Issue 4 Pg. 433-40 (May 2008) ISSN: 0969-8051 [Print] United States
• PMID: 18482680 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Radiopharmaceuticals
• Sodium Pertechnetate Tc 99m

Topics

• Animals
• Bacteria (virology)
• Bacterial Infections (diagnostic imaging)
• Bacteriophages (chemistry, pathogenicity)
• Disease Models, Animal
• Escherichia coli (virology)
• Host-Pathogen Interactions
• Infections (diagnostic imaging)
• Isotope Labeling (methods)
• Klebsiella pneumoniae (virology)
• Male
• Mice
• Pseudomonas aeruginosa (virology)
• Radionuclide Imaging
• Radiopharmaceuticals (chemistry, pharmacokinetics)
• Salmonella enterica (virology)
• Sodium Pertechnetate Tc 99m (chemistry, pharmacokinetics)
• Species Specificity
• Tissue Distribution